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Lung cancer AND CDK

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https://www.readbyqxmd.com/read/29360538/ccrk-is-a-novel-signalling-hub-exploitable-in-cancer-immunotherapy
#1
REVIEW
Myth T S Mok, Jingying Zhou, Wenshu Tang, Xuezhen Zeng, Antony W Oliver, Simon E Ward, Alfred S L Cheng
Cyclin-dependent kinase 20 (CDK20), or more commonly referred to as cell cycle-related kinase (CCRK), is the latest member of CDK family with strong linkage to human cancers. Accumulating studies have reported the consistent overexpression of CCRK in cancers arising from brain, colon, liver, lung and ovary. Such aberrant up-regulation of CCRK is clinically significant as it correlates with tumor staging, shorter patient survival and poor prognosis. Intriguingly, the signalling molecules perturbed by CCRK are divergent and cancer-specific, including the cell cycle regulators CDK2, cyclin D1, cyclin E and RB in glioblastoma, ovarian carcinoma and colorectal cancer, and KEAP1-NRF2 cytoprotective pathway in lung cancer...
January 21, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29311118/therapeutic-challenge-with-a-cdk-4-6-inhibitor-induces-an-rb-dependent-smac-mediated-apoptotic-response-in-non-small-cell-lung-cancer
#2
Chellappagounder Thangavel, Ettickan Boopathi, Yi Liu, Christopher McNair, Alex Haber, Maryna Perepelyuk, Anshul Bhardwaj, Sankar Addya, Adam Ertel, Sunday Shoyele, Ruth Birbe, Joseph M Salvino, Adam P Dicker, Karen E Knudsen, Robert B Den
The retinoblastoma tumor suppressor (RB), a key regulator of cell cycle progression and proliferation, is functionally suppressed in up to 50% of non-small cell lung cancer (NSCLC).  RB function is exquisitely controlled by a series of proteins including the CyclinD-CDK4/6 complex. In the current study, we interrogated the capacity of a CDK4/6 inhibitor, palbociclib, to activate RB function.   Experimental Design and Results: We employed multiple isogenic RB proficient and deficient NSCLC lines to interrogate the cytostatic and cytotoxic capacity of CDK 4/6 inhibition in vitro and in vivo  We demonstrate that while short term exposure to palbociclib induces cellular senescence, prolonged exposure results in inhibition of tumor growth...
January 8, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29276047/overcoming-resistance-to-the-thz-series-of-covalent-transcriptional-cdk-inhibitors
#3
Yang Gao, Tinghu Zhang, Hideki Terai, Scott B Ficarro, Nicholas Kwiatkowski, Ming-Feng Hao, Bandana Sharma, Camilla L Christensen, Edmond Chipumuro, Kwok-Kin Wong, Jarrod A Marto, Peter S Hammerman, Nathanael S Gray, Rani E George
Irreversible inhibition of transcriptional cyclin-dependent kinases (CDKs) provides a therapeutic strategy for cancers that rely on aberrant transcription; however, lack of understanding of resistance mechanisms to these agents will likely impede their clinical evolution. Here, we demonstrate upregulation of multidrug transporters ABCB1 and ABCG2 as a major mode of resistance to THZ1, a covalent inhibitor of CDKs 7, 12, and 13 in neuroblastoma and lung cancer. To counter this obstacle, we developed a CDK inhibitor, E9, that is not a substrate for ABC transporters, and by selecting for resistance, determined that it exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12...
December 15, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29237430/antitumor-effect-of-quercetin-on-y79-retinoblastoma-cells-via-activation-of-jnk-and-p38-mapk-pathways
#4
Haojie Liu, Ming Zhou
BACKGROUND: Quercetin (QCT) is a flavonol present in many vegetables, it is proved to show chemo preventive effect against lung, cervical, prostate, breast and colon cancer due to its anti-inflammatory, anti-tumor and anti-oxidant property. Looking into the reported chemo-preventive effect we speculated antitumor activity in retinoblastoma (RB) Y79 cells, we also studied the molecular mechanism for antitumor activity. METHODS: The effect of QCT on Y79 cell viability count was done by cell counting kit, cell cycle distribution, apoptosis studies and mitochondrial membrane potential was evaluated by flow cytometry...
December 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29177004/active-fraction-hs7-from-taiwanofungus-camphoratus-inhibits-akt-mtor-erk-and-stat3-pathways-and-induces-cdk-inhibitors-in-cl1-0-human-lung-cancer-cells
#5
I-Chun Lai, Gi-Ming Lai, Jyh-Ming Chow, Hsin-Lun Lee, Chuan-Feng Yeh, Chi-Han Li, Jiann-Long Yan, Shuang-En Chuang, Jacqueline Whang-Peng, Kuan-Jen Bai, Chih-Jung Yao
Background: The non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. In NSCLC, the oncogenic AKT-mTOR, ERK and STAT3 pathways are commonly dysregulated and have emerged as attractive targets for therapeutic developments. In a relatively limited subset of NSCLC, these pathways driven by mutant EGFR can be treated by the tyrosine kinase inhibitors (TKIs)-mediated targeted therapy. However, for the most NSCLC, more novel targeted agents are imperatively needed...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#6
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29116073/-differential-expression-of-an-ensemble-of-the-key-genes-involved-in-cell-cycle-regulation-in-lung-cancer
#7
G S Krasnov, G A Puzanov, A V Kudryavtseva, A A Dmitriev, A D Beniaminov, T T Kondratieva, V N Senchenko
Targeted cancer therapy directed at individual targets is often accompanied by the rapid development of drug resistance. The development of a new generation of antitumor drugs involves the search for many targets simultaneously to block or, conversely, restore their activity. In this regard, simultaneous analysis of gene expression in a complex network of interactions, primarily cell cycle control elements, is relevant for the search of specific molecular markers for the differential diagnosis of adenocarcinoma (ADC) and squamous cell lung cancer (SCC), as well as new targets for therapy...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28994315/first-line-treatment-disruption-among-post-menopausal-women-with-hr-her2-metastatic-breast-cancer-a-retrospective-us-claims-study
#8
Derek H Tang, Nanxin Li, Ella X Du, Miranda Peeples, Lihao Chu, Jipan Xie, Victoria Barghout
OBJECTIVE: This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. METHODS: Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database...
October 27, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28993193/%C3%AE-lipoic-acid-inhibits-human-lung-cancer-cell-proliferation-through-grb2-mediated-egfr-downregulation
#9
Lan Yang, Ya Wen, Guoqing Lv, Yuntao Lin, Junlong Tang, Jingxiao Lu, Manqiao Zhang, Wen Liu, Xiaojuan Sun
BACKGROUND: Alpha lipoic acid (α -LA) is a naturally occurring antioxidant and metabolic enzyme co-factor. Recently, α -LA has been reported to inhibit the growth of various cancer cells, but the precise signaling pathways that mediate the effects of α -LA on non-small cell lung cancer (NSCLC) development remain unclear. METHODS: The CCK-8 assay was used to assess cell proliferation in NSCLC cell lines after α -LA treatment. The expression of growth factor receptor-bound protein 2 (Grb2), cyclin-dependent kinase (CDK)-2, CDK4, CDK6, Cyclin D3, Cyclin E1, Ras, c-Raf, epidermal growth factor receptor (EGFR), ERK1/2 and activated EGFR and ERK1/2 was evaluated by western blotting...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28869605/suppression-of-sirt1-sensitizes-lung-cancer-cells-to-wee1-inhibitor-mk-1775-induced-dna-damage-and-apoptosis
#10
G Chen, B Zhang, H Xu, Y Sun, Y Shi, Y Luo, H Jia, F Wang
Lung cancer treatment remains a challenge for clinical practice and new therapeutic approaches are urgently needed. Loss of functional WEE1 kinase causes DNA replication stress, DNA damage and unscheduled mitotic entry due to elevated CDK activity. The selective WEE1 inhibitor MK-1775 synergize with DNA-damaging agent to inhibit cancer cell growth. Here we report that inhibition of Sirt1 deacetylase through small interfering RNA or selective inhibitor Ex527 greatly enhances MK-1775-induced growth inhibition and apoptosis in human lung cancer cells...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28859099/acacetin-enhances-the-therapeutic-efficacy-of-doxorubicin-in-non-small-cell-lung-carcinoma-cells
#11
Reenu Punia, Komal Raina, Rajesh Agarwal, Rana P Singh
BACKGROUND: Anthracyclines are efficient and potent agents to treat broad range of cancers but cytotoxicity induced by them limits their use in therapeutics. Use of plant-derived agents help to prevent or delay the process of cancer progression and their combination increases the anti-cancer potential of mainstream compound. However, multidrug resistance is major cause of treatment failure in cancer patients. PURPOSE: In this study, combination treatments of fisetin or acacetin with doxorubicin were explored for their potential synergistic effect on non-small-cell lung carcinoma (NSCLC) cells...
2017: PloS One
https://www.readbyqxmd.com/read/28463960/phase-i-dose-escalation-studies-of-roniciclib-a-pan-cyclin-dependent-kinase-inhibitor-in-advanced-malignancies
#12
MULTICENTER STUDY
Rastislav Bahleda, Juneko E Grilley-Olson, Ramaswamy Govindan, Fabrice Barlesi, Laurent Greillier, Maurice Perol, Isabelle Ray-Coquard, Dirk Strumberg, Beate Schultheis, Grace K Dy, Gérard Zalcman, Glen J Weiss, Annette O Walter, Martin Kornacker, Prabhu Rajagopalan, David Henderson, Hendrik Nogai, Matthias Ocker, Jean-Charles Soria
BACKGROUND: To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). METHODS: Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28323486/enterolactone-induces-g1-phase-cell-cycle-arrest-in-nonsmall-cell-lung-cancer-cells-by-downregulating-cyclins-and-cyclin-dependent-kinases
#13
Shireen Chikara, Kaitlin Lindsey, Harsharan Dhillon, Sujan Mamidi, Jeffrey Kittilson, Melpo Christofidou-Solomidou, Katie M Reindl
Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG), which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anticancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study, we investigated the anticancer effects of EL for several nonsmall cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners...
May 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/27815686/cdk4-in-lung-and-head-and-neck-cancers-in-old-age-evaluation-as-a-biomarker
#14
J Banerjee, R Pradhan, A Gupta, R Kumar, V Sahu, A D Upadhyay, P Chaterjee, S Dwivedi, S Dey, A B Dey
BACKGROUND: Cyclin dependent kinases (CDK) are key factors in promoting the initiation and development of tumors. These kinases are important for maintenance of mitochondrial biogenesis and imbalance in their expression in old age may lead to the oxidative stress. Lung cancer (LC), and head and neck squamous cell carcinoma (HNSCC) are two very prominent cancers in older Indians. Both the cancers are showing increasing trend in older population. The present study assessed serum concentration of one of the kinases; CDK4 in older LC and HNSCC patients...
May 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27775798/the-role-of-znrf2-in-the-growth-of-non-small-cell-lung-cancer
#15
X-F Zhang, Z-Q Guo, C-C Zhao, C-Y Xu, M Han, C Li, Z Wang
OBJECTIVE: ZNRF2 belongs to ubiquitin ligases of the RING superfamily, and has been recently shown to be regulated by Akt to interact with a Mechanistic target of rapamycin (mTor). Nevertheless, a role of ZNRF2 in tumorigenesis, especially in non-small cell lung cancer (NSCLC), is unknown. Here, we assessed ZNRF2 expression in NSCLC. PATIENTS AND METHODS: We examined ZNRF2 levels by Western blot using NSCLC specimens, compared to the paired non-tumor controls. We also examined the effects of ZNRF2 on cell growth and cell survival in the presence of fluorouracil...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27636029/downregulation-of-a-novel-human-gene-rogdi-increases-radiosensitivity-in-cervical-cancer-cells
#16
Yi-Fan Chen, Jonathan J Cho, Tsai-Hua Huang, Chao-Neng Tseng, Eng-Yen Huang, Chung-Lung Cho
ROGDI is a protein that contains a leucine zipper domain and may be involved in cell proliferation. In addition, ROGDI is associated with genome stability by regulating the activity of a DNA damage marker, γ-H2AX. The role of ROGDI in tumor radiosensitization has not been investigated. Previous studies have indicated that radiosensitivity is associated with DNA repair and the cell cycle. In general, the G2/M DNA damage checkpoint is more sensitive to radiation, whereas the G1/S phase transition is more resistant to radiation...
August 12, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27558135/a-synthetic-dosage-lethal-genetic-interaction-between-cks1b-and-plk1-is-conserved-in-yeast-and-human-cancer-cells
#17
Robert J D Reid, Xing Du, Ivana Sunjevaric, Vinayak Rayannavar, John Dittmar, Eric Bryant, Matthew Maurer, Rodney Rothstein
The CKS1B gene located on chromosome 1q21 is frequently amplified in breast, lung, and liver cancers. CKS1B codes for a conserved regulatory subunit of cyclin-CDK complexes that function at multiple stages of cell cycle progression. We used a high throughput screening protocol to mimic cancer-related overexpression in a library of Saccharomyces cerevisiae mutants to identify genes whose functions become essential only when CKS1 is overexpressed, a synthetic dosage lethal (SDL) interaction. Mutations in multiple genes affecting mitotic entry and mitotic exit are highly enriched in the set of SDL interactions...
October 2016: Genetics
https://www.readbyqxmd.com/read/27550941/dinaciclib-induces-anaphase-catastrophe-in-lung-cancer-cells-via-inhibition-of-cyclin-dependent-kinases-1-and-2
#18
Alexey V Danilov, Shanhu Hu, Bernardo Orr, Kristina Godek, Lisa Maria Mustachio, David Sekula, Xi Liu, Masanori Kawakami, Faye M Johnson, Duane A Compton, Sarah J Freemantle, Ethan Dmitrovsky
Despite advances in targeted therapy, lung cancer remains the most common cause of cancer-related mortality in the United States. Chromosomal instability is a prominent feature in lung cancer and, because it rarely occurs in normal cells, it represents a potential therapeutic target. Our prior work discovered that lung cancer cells undergo anaphase catastrophe in response to inhibition of cyclin-dependent kinase 2 (CDK2), followed by apoptosis and reduced growth. In this study, the effects and mechanisms of the multi-CDK inhibitor dinaciclib on lung cancer cells were investigated...
November 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27461583/a-novel-combinatorial-strategy-using-seliciclib-%C3%A2-and-belinostat-%C3%A2-for-eradication-of-non-small-cell-lung-cancer-via-apoptosis-induction-and-bid-activation
#19
Pei-Shi Ong, Lingzhi Wang, Deborah Miao-Hui Chia, Jolyn Yu-Xin Seah, Li-Ren Kong, Win-Lwin Thuya, Arunachalam Chinnathambi, Jie-Ying Amelia Lau, Andrea Li-Ann Wong, Wei-Peng Yong, Daiwen Yang, Paul Chi-Lui Ho, Gautam Sethi, Boon-Cher Goh
With conventional anticancer agents for non-small cell lung cancer (NSCLC) reaching therapeutic ceiling, the novel combination using histone deacetylase inhibitor, PXD101 (Belinostat(®)), and CDK inhibitor, CYC202 (Seliciclib(®)), was investigated as an alternative anticancer strategy. At clinically achievable concentration of CYC202 (15 µM), combination therapy resulted in significant reduction in cell proliferation (IC50 = 3.67 ± 0.80 µM, p < 0.05) compared with PXD101 alone (IC50 = 6...
October 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27217383/efficacy-and-safety-of-abemaciclib-an-inhibitor-of-cdk4-and-cdk6-for-patients-with-breast-cancer-non-small-cell-lung-cancer-and-other-solid-tumors
#20
Amita Patnaik, Lee S Rosen, Sara M Tolaney, Anthony W Tolcher, Jonathan W Goldman, Leena Gandhi, Kyriakos P Papadopoulos, Muralidhar Beeram, Drew W Rasco, John F Hilton, Aejaz Nasir, Richard P Beckmann, Andrew E Schade, Angie D Fulford, Tuan S Nguyen, Ricardo Martinez, Palaniappan Kulanthaivel, Lily Q Li, Martin Frenzel, Damien M Cronier, Edward M Chan, Keith T Flaherty, Patrick Y Wen, Geoffrey I Shapiro
UNLABELLED: We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in a multicenter study including phase I dose escalation followed by tumor-specific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, and colorectal cancer. A total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts...
July 2016: Cancer Discovery
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